Viruses which induce tumors in mammals are widespread. Indeed, there are over sixty known types of human papillomaviruses (HPV) which are DNA viruses. These viruses can induce the production of tumors. Some of these HPV's have been associated with benign tumors, such as common warts, while others have been strongly implicated as etiologic agents in dysplasia and carcinomas in the oral and genital mucosa of the infected mammal.
Warts are a very common skin lesion in humans and are caused by various human papillomaviruses (DNA virus). Each virus is related to a specific clinical presentation of the wart. Warts are infectious and can be autoinoculated and spread to other individuals by direct contact.
Verrucae warts have a rough surface, are lumpy and typically flesh colored. Finger-like projections and sometimes dark specks are present, which are the result of thrombosed capillaries. Usually these warts are found on the face and scalp. Plantar warts are found on the planter surface of the feet and can be deep and painful. These warts occur singularly, in clusters or be spread over a wide area. Flat warts are typically small, flat-topped, flesh colored papules that occur primarily on the face, hands and forearms. Usually the surface of the wart is smooth and they may appear in the hundreds. Genital warts are soft, flesh colored or slightly pigmented and occur in the genitalia of the mammal and are sexually transmitted. Chronic infections of the viruses that cause genital warts in women are a serious problem as intra epithelial neoplasia or squamous cell carcinoma may develop. See Oski et al., Princ. Pract. Pediatrics, 2nd ed., pp. 789-790.
There are various therapies for the treatment of warts, but none are considered truly effective as they typically fail to totally cure the lesions and do not prevent recurrence. A discussion of presently accepted therapies can be found in Stone, 1995, Cl. Infec. Diseases, Suppl. 20, pp. 991-997 and Sterling, 1995, Practioner, Jan. 239(1546), pp. 44-47. Numerous compositions are presently marketed for wart removal. One such product is Occlusal.RTM.-HP marketed by the GenDerm Corporation of Lincolnshire, Ill. This product is a 17% solution of salicylic acid in a polyacrylic vehicle. The Shering-Plough Company of Memphis, Tenn. produces and markets a product known as Duo Film.RTM. which is a patch containing salicylic acid. The product literature recommends that the wart be washed and dried prior to the application of a medicated patch which contains 40% salicylic acid. This patch is then covered with an additional bandage and the procedure is repeated every 48 hours until the wart is gone, which sometimes takes up to 12 weeks.
Recently, it has also been observed that individuals with depressed immune systems, such as sufferers of Acquired Immune Deficiency Syndrome (AIDS), are prone to HPV infections which can result in tumor growth over their entire bodies, resulting in great mental and physical distress to the afflicted individual.
Current modalities for the treatment of viral-induced tumors involve the removal of the tumor by either: (1) surgical intervention (laser or operative); (2) the application of organic acids, such as glacial acetic acid and/or salicylic acid and lactic acid to "burn" the tumor away; (3) the injection into the tumor of an anti-tumor vaccine prepared from ground tumors; and to a lesser extent, (4) the use of a drug, such as podophyllin, interferons and fluorouracil or 5-FU; and (5) freezing.
While being useful for removing the viral-induced tumor, the current treatment modalities still suffer from one or more of the following drawbacks: (1) they can result in the destruction of healthy uninfected tissue; (2) they can result in scarring and disfigurement; (3) they can result in discomfort to the mammal being treated thereby; (4) they can result in necrosis of the tumor and the surrounding tissue may can result in a secondary infection which may require treatment with an antibiotic; and (5) they do not always result in the destruction of latent viral DNA which may be maintained in surrounding tissues. Furthermore with these conventional treatments, subjects suffer from significant local, and at times, systemic side effects, incomplete resolution and frequent recurrences of the tumors, and of course, the expense incurred.
It is also known that phototherapy is used for removing laryngeal papillomatosis tumors. While such phototherapy reduces tumor growth by about 50%, it also results in a generalized skin photosensitivity for at least six weeks, as well as other minor reactions. Despite the apparent success of this technique, the presence of latent viral DNA is nonetheless still maintained in the surrounding tissues.
U.S. Pat. No. 5,073,630 discloses a polymeric anhydride of magnesium and ammonium phospholinoleate with antiviral, antineoplastic and immunostimulant properties. This antiviral agent is produced from a selected line of Aspergillus sp. However, the compound is insoluble in water and possesses a high molecular weight (316,000 daltons). Recovery of the compound from the culture is problematic and costly.
U.S. Pat. No. 5,562,900 discloses a composition for the treatment of viral-induced tumors comprising an Aspergillus fermentation extract or a derivative thereof in a pharmaceutically acceptable carrier.
U.S. Pat. No. 5,541,058 discloses an in vitro method for testing the effectiveness of antiviral agents. More specifically, this patent relates to a method for screening anti-papillomavirus drugs which can interfere with the early and maintenance stages of papillomavirus infection. The teachings of this patent are incorporated herein by reference.
U.S. Pat. No. 5,332,215 discloses a method for inhibiting viral proliferation by preventing or inhibiting viral replication or killing the virus on contact. The method uses serine protease inhibitors, their analogs, salts, conjugates or derivatives.
An article by B. M. Lawrence entitled "Progress in Essential Oils", Perfumer & Flavorist, Vol. 16, 49-58 (1991) reviews the work of several investigators on the chemical composition of sandalwood oil. This article reports on several of the oxidation products of the oil and compares the composition of Chinese sandalwood oil and Indian sandalwood oil. The santalol content (santalol, cis-.alpha. and cis-.beta., comprises about 50 and 20% respectively by weight of sandalwood oil) of various species of the genus Santalum, are also disclosed. This article makes no suggestion that sandalwood oil would be effective in treating the common wart in humans.
An article by Dwivedi et al. entitled, "Chemopreventive effects of sandalwood oil on skin papillomas in mice" in the European Journal of Cancer Prevention 1997; 6(4): 399-401, reports that the essential oil, emulsion or paste of sandalwood (Santalum album L) has been used in India as an ayruvedic medicinal agent. In his investigation, a 5% w/v solution of sandalwood oil in acetone was shown to be a chemopreventive agent against 7, 12-dimethylbenz(a)anthracene initiated and 12-O-tetracecanoyl phorbol-13-acetate promoted skin papillomas in CD1 mice. The author suggests that sandalwood oil could be an effective chemopreventive agent against skin cancer.
None of these references suggest or disclose the use of sandalwood oil or a soap containing sandalwood oil as an agent for the treatment of human papillomavirus-induced tumors. There presently exists in the medical community a need for improved methods and compositions which provide prophylactic and/or therapeutic treatment of viral-induced tumors such as warts in humans. The present invention fills that need of the medical community.